Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease.
Date
2016-06-01Author
Orlando, G
Law, PJ
Palin, K
Tuupanen, S
Gylfe, A
Hänninen, UA
Cajuso, T
Tanskanen, T
Kondelin, J
Kaasinen, E
Sarin, A-P
Kaprio, J
Eriksson, JG
Rissanen, H
Knekt, P
Pukkala, E
Jousilahti, P
Salomaa, V
Ripatti, S
Palotie, A
Järvinen, H
Renkonen-Sinisalo, L
Lepistö, A
Böhm, J
Mecklin, J-P
Al-Tassan, NA
Palles, C
Martin, L
Barclay, E
Tenesa, A
Farrington, S
Timofeeva, MN
Meyer, BF
Wakil, SM
Campbell, H
Smith, CG
Idziaszczyk, S
Maughan, TS
Kaplan, R
Kerr, R
Kerr, D
Buchanan, DD
Win, AK
Hopper, J
Jenkins, M
Lindor, NM
Newcomb, PA
Gallinger, S
Conti, D
Schumacher, F
Casey, G
Taipale, J
Cheadle, JP
Dunlop, MG
Tomlinson, IP
Aaltonen, LA
Houlston, RS
Type
Journal Article
Metadata
Show full item recordAbstract
To identify new risk loci for colorectal cancer (CRC), we conducted a meta-analysis of seven genome-wide association studies (GWAS) with independent replication, totalling 13 656 CRC cases and 21 667 controls of European ancestry. The combined analysis identified a new risk association for CRC at 2q35 marked by rs992157 (P = 3.15 × 10-8, odds ratio = 1.10, 95% confidence interval = 1.06-1.13), which is intronic to PNKD (paroxysmal non-kinesigenic dyskinesia) and TMBIM1 (transmembrane BAX inhibitor motif containing 1). Intriguingly this susceptibility single-nucleotide polymorphism (SNP) is in strong linkage disequilibrium (r2 = 0.90, D' = 0.96) with the previously discovered GWAS SNP rs2382817 for inflammatory bowel disease (IBD). Following on from this observation we examined for pleiotropy, or shared genetic susceptibility, between CRC and the 200 established IBD risk loci, identifying an additional 11 significant associations (false discovery rate [FDR]) < 0.05). Our findings provide further insight into the biological basis of inherited genetic susceptibility to CRC, and identify risk factors that may influence the development of both CRC and IBD.
Collections
Subject
Humans
Colorectal Neoplasms
Inflammatory Bowel Diseases
Genetic Predisposition to Disease
Muscle Proteins
Membrane Proteins
Risk Factors
Linkage Disequilibrium
Polymorphism, Single Nucleotide
Asian Continental Ancestry Group
European Continental Ancestry Group
Female
Male
Apoptosis Regulatory Proteins
Genome-Wide Association Study
Genetic Pleiotropy
Research team
Cancer Genomics
Language
eng
Date accepted
2016-03-14
License start date
2016-06
Citation
Human molecular genetics, 2016, 25 (11), pp. 2349 - 2359
Publisher
OXFORD UNIV PRESS